Fetal and neonatal alloimmune thrombocytopenia: novel mechanisms and therapeutic approaches

Platelets are small blood cells that are responsible for the arrest of bleeding at the site of vessel injury. A low platelet count is called thrombocytopenia. Antibodies to fetal platelets can be induced in the mother by proteins called antigens on platelets, which are inherited from the father but lacking in the mother. These maternal antibodies can cross the placenta and damage fetal platelets leading to a disease called Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT). This disease occurs in 0.5-1.5/1,000 liveborn neonates without including miscarriages. Reports have suggested that miscarriage may occur in 10-30% of affected fetuses. The major risk associated with FNAIT is severe bleeding, particularly in the brain (intracranial haemorrhage). Currently, the pathogenesis of FNAIT is largely unknown and effective therapy is not available. We plan to use our newly developed FNAIT mouse models to study: 1) how a mother generates antibodies to different fetal platelet antigens, how these antibodies affect fetal platelet function and clearance that may lead to miscarriage; 2) whether these antibodies also target fetal vessels, and vessels and trophoblasts in placenta as well as fetal stem cells, which may enhance bleeding, inhibit fetal growth, and affect fetal liver development; and 3) whether we can prevent and treat this disease more efficiently by using IVIG and our newly developed prophylaxis, anti-FcRn and anti-NK cell therapies. This study will provide significant information for both the pathogenesis and treatment of FNAIT.

NI, Heyu

St. Michael's Hospital

Canadian Blood Services-CIHR Partnership Operating Grant Program

Ontario

$471,393